BODIPY-pyrene donor-acceptor sensitizers for triplet-triplet annihilation upconversion: the impact of the BODIPY-core on upconversion efficiency.

Triplet-triplet annihilation upconversion (TTA-UC) is an important type of optical process with applications in biophotonics, solar energy harvesting and photochemistry. In most of the TTA-UC systems, the formation of triplet excited states takes place via spin-orbital interactions promoted by heavy atoms. Given the crucial role of heavy atoms (especially noble metals, such as Pd and Pt) in promoting intersystem crossing (ISC) and, therefore, in production of UC luminescence, the feasibility of using more readily available and inexpensive sensitizers without heavy atoms remains a challenge. Here, we investigated sensitization of TTA-UC using BODIPY-pyrene heavy-atom-free donor-acceptor dyads with different numbers of alkyl groups in the BODIPY scaffold. The molecules with four and six alkyl groups are unable to sensitize TTA-UC in the investigated solvents (tetrahydrofuran (THF) and dichloromethane (DCM)) due to negligible ISC. In contrast, the dyad with two methyl groups in the BODIPY scaffold and the dyad with unsubstituted BODIPY demonstrate efficient intersystem crossing (ISC) of 49-58%, resulting in TTA-UC with quantum yields of 4.7% and 6.9%, respectively. The analysis of the elementary steps of the TTA-UC process indicates that heavy-atom-free donor-acceptor dyads are less effective than their noble metal counterparts, but may equal them in the future if the right combination of solvent, donor-acceptor sensitizer structure, and new luminescent molecules as TTA-UC emitters can be found.

Quantitative Structure-Property Relationship Modelling for the Prediction of Singlet Oxygen Generation by Heavy-Atom-Free BODIPY Photosensitizers*.

Heavy-atom-free sensitizers forming long-living triplet excited states via the spin-orbit charge transfer intersystem crossing (SOCT-ISC) process have recently attracted attention due to their potential to replace costly transition metal complexes in photonic applications. The efficiency of SOCT-ISC in BODIPY donor-acceptor dyads, so far the most thoroughly investigated class of such sensitizers, can be finely tuned by structural modification. However, predicting the triplet state yields and reactive oxygen species (ROS) generation quantum yields for such compounds in a particular solvent is still very challenging due to a lack of established quantitative structure-property relationship (QSPR) models. In this work, the available data on singlet oxygen generation quantum yields (ΦΔ ) for a dataset containing >70 heavy-atom-free BODIPY in three different solvents (toluene, acetonitrile, and tetrahydrofuran) were analyzed. In order to build reliable QSPR model, a series of new BODIPYs were synthesized that bear different electron donating aryl groups in the meso position, their optical and structural properties were studied along with the solvent dependence of singlet oxygen generation, which confirmed the formation of triplet states via the SOCT-ISC mechanism. For the combined dataset of BODIPY structures, a total of more than 5000 quantum-chemical descriptors was calculated including quantum-chemical descriptors using density functional theory (DFT), namely M06-2X functional. QSPR models predicting ΦΔ values were developed using multiple linear regression (MLR), which perform significantly better than other machine learning methods and show sufficient statistical parameters (R=0.88-0.91 and q2 =0.62-0.69) for all three solvents. A small root mean squared error of 8.2 % was obtained for ΦΔ values predicted using MLR model in toluene. As a result, we proved that QSPR and machine learning techniques can be useful for predicting ΦΔ values in different media and virtual screening of new heavy-atom-free BODIPYs with improved photosensitizing ability.

In vitro cytotoxicity of a library of BODIPY-anthracene and -pyrene dyads for application in photodynamic therapy.

The facile synthesis and in vitro activity of a library of heavy atom-free BODIPY-anthracene, -pyrene dyads (BAD-13-BPyrD-19) and a control (BODIPY 20) are reported. We demonstrate that singlet oxygen produced from dyad triplet states formed from charge-separated states is sufficient to induce cytotoxicity in human breast cancer cells (MDA-MB-468) at micromolar concentrations. The compounds in this series are promising candidates for photodynamic therapy, especially BAD-17 which displays significant photocytotoxicity (15% cell viability) at a concentration of 5 × 10-7 M, with minimal toxicity (89% cell viability) in the absence of light.

Heavy-atom-free BODIPY photosensitizers with intersystem crossing mediated by intramolecular photoinduced electron transfer.

Organic photosensitizers possessing efficient intersystem crossing (ISC) and forming long-living triplet excited states, play a crucial role in a number of applications. A common approach in the design of such dyes relies on the introduction of heavy atoms (e.g. transition metals or halogens) into the structure, which promote ISC via spin-orbit coupling interaction. In recent years, alternative methods to enhance ISC have been actively studied. Among those, the generation of triplet excited states through photoinduced electron transfer (PET) in heavy-atom-free molecules has attracted particular attention because it allows for the development of photosensitizers with programmed triplet state and fluorescence quantum yields. Due to their synthetic accessibility and tunability of optical properties, boron dipyrromethenes (BODIPYs) are so far the most perspective class of photosensitizers operating via this mechanism. This article reviews recently reported heavy-atom-free BODIPY donor-acceptor dyads and dimers which produce long-living triplet excited states and generate singlet oxygen. Structural factors which affect PET and concomitant triplet state formation in these molecules are discussed and the reported data on triplet state yields and singlet oxygen generation quantum yields in various solvents are summarized. Finally, examples of recent applications of these systems are highlighted.

Control of triplet state generation in heavy atom-free BODIPY-anthracene dyads by media polarity and structural factors.

A family of heavy atom-free BODIPY-anthracene dyads (BADs) exhibiting triplet excited state formation from charge-transfer states is reported. Four types of BODIPY scaffolds, different in the alkyl substitution pattern, and four anthracene derivatives have been used to access BADs. Fluorescence and intersystem crossing (ISC) in these dyads depend on donor-acceptor couplings and can be accurately controlled by substitution or media polarity. Under conditions that do not allow charge transfer (CT), the dyads exhibit fluorescence with high quantum yields. Formation of charge-transfer states triggers ISC and the formation of long-lived triplet excited states in the dyads. The excited state properties were studied by steady-state techniques and ultrafast pump-probe spectroscopy to determine the parameters of the observed processes. Structural information for various BADs was derived from single crystal X-ray structure determinations alongside DFT molecular geometry optimization, revealing the effects of mutual orientation of subunits on the photophysical properties. The calculations showed that alkyl substituents on the BODIPY destabilize CT states in the dyads, thus controlling the charge transfer between the subunits. The effect of the dyad structure on the ISC efficiency was considered at the M06-2X level of theory, and a correlation between mutual orientation of the subunits and the energy gap between singlet and triplet CT states was studied using a multireference CASSCF method.

Generation of Triplet Excited States via Photoinduced Electron Transfer in meso-anthra-BODIPY: Fluorogenic Response toward Singlet Oxygen in Solution and in Vitro.

Heavy atom-free BODIPY-anthracene dyads (BADs) generate locally excited triplet states by way of photoinduced electron transfer (PeT), followed by recombination of the resulting charge-separated states (CSS). Subsequent quenching of the triplet states by molecular oxygen produces singlet oxygen (1O2), which reacts with the anthracene moiety yielding highly fluorescent species. The steric demand of the alkyl substituents in the BODIPY subunit defines the site of 1O2 addition. Novel bis- and tetraepoxides and bicyclic acetal products, arising from rearrangements of anthracene endoperoxides were isolated and characterized. 1O2 generation by BADs in living cells enables visualization of the dyads distribution, promising new imaging applications.

Delayed release singlet oxygen sensitizers based on pyridone-appended porphyrins.

A new type of porphyrin photosensitizer capable of generating singlet oxygen upon irradiation, storing it through binding to pyridone subunits, followed by slow release at 20-40 °C, is reported. The timescale of singlet oxygen release can be varied depending on the pyridone group substitution pattern, forming endoperoxides of different stabilities. Modified tetra- and octa-substituted pyridone-porphyrins showed solubility in water, allowing for straightforward delivery into cells. The effect of delayed singlet oxygen formation due to endoperoxide decomposition was demonstrated on cancer cells in vitro.

Protection of densely populated excited triplet state ensembles against deactivation by molecular oxygen.

This critical review discusses different approaches towards protection of photoactive materials based on triplet excited state ensembles against deactivation by molecular oxygen though quenching and photooxidation mechanisms. Passive protection, based on the application of barrier materials for packaging, sealing, or encapsulation of the active substances, which prevent oxygen molecules from penetration and physical contact with excited states and active protection, based on the application of oxygen scavenging species are compared. Efficiencies of different approaches together with examples and prospects of their applications are outlined.

meso-Tetraphenylporphyrin with a pi-system extended by fusion with anthraquinone.

Fusion with a 9,10-anthraquinone moiety was achieved to extend porphyrin's π-system. A bridged dihydroisoindole derivative was used to prepare the corresponding meso-tetraphenyltetraanthraquinonoporphyrin (Ph4TAQP) via a thermal retro-Diels-Alder reaction. The basic optical properties of the prepared new anthraquinonoporphyrin and its complexes with Zn and Pd were studied.

Reversible oxygen addition on a triplet sensitizer molecule: protection from excited state depopulation.

We demonstrate that photoactivated oxygen addition to diphenylanthracene moities can be used as a tool for protection of porphyrin's phosphorescence against oxygen quenching. Phosphorescent palladium(II) tetrabenzoporphyrin, covalently linked to four diphenylanthracene moieties, was synthesized and studied. Upon irradiation with ambient light or red laser in solution in air, addition of oxygen and formation of the corresponding endoperoxides were observed. Heating of the irradiated samples afforded the parent porphyrin material.

Triplet sensitization enables bidirectional isomerization of diazocine with 130 nm redshift in excitation wavelengths.

Diazocines are bridged azobenzenes with phenyl rings connected by a CH2-CH2 group. Despite this rather small structural difference, diazocine exhibits improved properties over azobenzene as a photoswitch and most importantly, its Z configuration is more stable than the E isomer. Herein, we reveal yet another unique feature of this emerging class of photoswitches. In striking contrast to azobenzenes and other photochromes, diazocine can be selectively switched in E → Z direction and most intriguingly from its thermodynamically stable Z to metastable E isomer upon successive excitation of two different triplet sensitizers present in solution at the same time. This approach leads to extraordinary large redshift of excitation wavelengths to perform isomerization i.e. from 400 nm blue to 530 nm green light (Z → E) and from 530 nm green to 740 nm far-red one (E → Z), which falls in the near-infrared window in biological tissue. Therefore, this work opens up of potential avenues for utilizing diazocines for example in photopharmacology, smart materials, light energy harvesting/storage devices, and out-of-equilibrium systems.

Tetraaryltetraanthra[2,3]porphyrins: synthesis, structure, and optical properties.

A synthetic route to symmetrical tetraaryltetraanthra[2,3]porphyrins (Ar(4)TAPs) was developed. Ar(4)TAPs bearing various substituents in meso-phenyls and anthracene residues were prepared from the corresponding pyrrolic precursors. The synthesized porphyrins possess high solubility and exhibit remarkably strong absorption bands in the near-infrared region (790-950 nm). The scope of the method, selection of the peripheral substituents, choice of the metal, and their influence on the optical properties are discussed together with the first X-ray crystallographic data for anthraporphyrin.

Extracellular Particles as Carriers of Cholesterol Not Associated with Lipoproteins.

Exosomes and exomeres are the smallest microparticles ranging from 20 to 130 nm in diameter. They are found in almost all biological fluids. Exosomes and exomeres are of considerable interest since they can be involved in intercellular signaling and are biological markers of the state of cells, which can be used for diagnostics. The nomenclature of exosomes remains poorly developed. Most researchers try to classify them based on the mode of formation, physicochemical characteristics, and the presence of tetrasporin markers CD9, CD63, and CD81. The data presented in this work show that although exomeres carry tetrasporin biomarkers, they differ from exosomes strongly in lipid composition, especially in cholesterol content. The production of exomeres by cells is associated with the synthesis of cholesterol in cells and is expressed or suppressed by regulators of the synthesis of mevalonate, an intermediate product of cholesterol metabolism. In addition, the work shows that the concentration of extracellular particles in the body correlates with the concentration of cholesterol in the plasma, but weakly correlates with the concentration of cholesterol in lipoproteins. This suggests that not all plasma cholesterol is associated with lipoproteins, as previously thought.

Ruthenium(II) complexes with phosphonate-substituted phenanthroline ligands: synthesis, characterization and use in organic photocatalysis.

Ru(II) complexes with polypyridyl ligands play a central role in the development of photocatalytic organic reactions. This work is aimed at the structural modification of such complexes to increase their photocatalytic efficiency and adapt them for the preparation of reusable photocatalytic systems. Nine [Ru(phen)(bpy)2]2+-type complexes (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline) (Ru-Pcat) bearing the P(O)(OEt)2 substituent attached to the phen core directly or through a 1,4-phenylene linker were synthesized and characterized by spectroscopic and electrochemical techniques. The coordination mode of phen ligands was confirmed by single crystal X-ray analysis. The (spectro)electrochemical data show that the first electron transfer in Ru-Pcat takes place on the phen ligand. The emission maxima and quantum yields are strongly affected by the substitution pattern, reaching the far-red region (697 nm) for Ru-3,8P2. The singlet oxygen quantum yields of Ru-Pcat were evaluated using the chemical trapping method. Finally, the photocatalytic performance of Ru-Pcat in the oxidation of sulfides with molecular oxygen was investigated. Both dialkyl and alkyl aryl sulfides were quantitatively transformed into sulfoxides under irradiation with a blue LED in the acetonitrile-water mixture (10 : 1) using a low loading of 0.005-0.05 mol% Ru(II) photocatalysts. To rationalize the effect of phosphonate substituents on the photocatalytic efficiency, comparative kinetic studies of (1) 4-nitrothioanisole oxidation proceeding predominantly via the electron transfer pathway and (2) oxidation of dibutyl sulfide wherein singlet oxygen serves as an oxidant have been performed. It was demonstrated that complexes with the P(O)(OEt)2 substituent at positions 4 and 7 outperform the benchmark photocatalyst Ru-(bpy)3 and the parent complex Ru-phen in the reactions proceeding through electron transfer (reductive quenching photocatalytic cycle). The TON in the oxidation of 4-methoxythioanisole was found to be as high as 1 000 000 that is, to our knowledge, the highest among previously reported photocatalysts. In contrast, upon separating the P(O)(OEt)2 group and the phen core with the 1,4-phenylene linker, singlet oxygen quantum yields significantly increase that favors reactions proceeding through energy transfer (the oxidation of dibutyl sulfide in our case). Thus, both series of Ru(II) complexes prepared in this work are promising for the improvement of known photocatalytic reactions and the development of new transformations.

Expanding excitation wavelengths for azobenzene photoswitching into the near-infrared range via endothermic triplet energy transfer.

Developing azobenzene photoswitches capable of selective and efficient photoisomerization by long-wavelength excitation is an enduring challenge. Herein, rapid isomerization from the Z- to E-state of two ortho-functionalized bistable azobenzenes with near-unity photoconversion efficiency was driven by triplet energy transfer upon red and near-infrared (up to 770 nm) excitation of porphyrin photosensitizers in catalytic micromolar concentrations. We show that the process of triplet-sensitized isomerization is efficient even when the sensitizer triplet energy is substantially lower (>200 meV) than that of the azobenzene used. This makes the approach applicable for a wide variety of sensitizer-azobenzene combinations and enables the expansion of excitation wavelengths into the near-infrared spectral range. Therefore, indirect excitation via endothermic triplet energy transfer provides efficient and precise means for photoswitching upon 770 nm near-infared light illumination with no chemical modification of the azobenzene chromophore, a desirable feature in photocontrollable biomaterials.

Pi-extended dipyrrins capable of highly fluorogenic complexation with metal ions.

The synthesis and properties of a new family of pi-extended dipyrrins capable of forming brightly fluorescent complexes with metal ions are reported. The metal complexes possess tunable spectral bands and exhibit different emission properties depending on the mode of metal coordination.

Determination of Upconversion Quantum Yields Using Charge-Transfer State Fluorescence of Heavy-Atom-Free Sensitizer as a Self-Reference.

The efficiency of photon upconversion via triplet-triplet annihilation is characterized by an upconversion quantum yield (ΦUC); however, uncertainties remain for its determination. Here, we present a new approach for the relative measurement of ΦUC for green-to-blue upconversion using BODIPY-pyrene donor-acceptor dyad (BD1) as a heavy-atom-free triplet sensitizer. This new approach exploits broad fluorescence from a charge-transfer (CT) state of BD1, which possesses (i) a significant Stokes shift of 181 nm in dichloromethane and (ii) a comparably high CT-fluorescence quantum yield (Φref = 7.0 ± 0.2%), which is independent from oxygen presence and emitter (perylene) concentration while also exhibiting a linear intensity dependence. On the basis of this, we developed an upconversion reference using the BD1 sensitizer mixed with perylene (1 × 10-5 M/1 × 10-4 M) in dichloromethane. With this reference system, we investigated the performance of three BODIPY donor-acceptor dyads in the upconversion process and achieved one of the highest ΦUC of 6.9 ± 0.2% observed for heavy-atom-free sensitizers to date.

Effects of structural deformations on optical properties of tetrabenzoporphyrins: free-bases and Pd complexes.

A recently developed method of synthesis of pi-extended porphyrins made it possible to prepare a series of tetrabenzoporphyrins (TBP) with different numbers of meso-aryl substituents. The photophysical parameters of free-bases and Pd complexes of meso-unsubstituted TBP's, 5,15-diaryl-TBP's (Ar2TBP's) and 5,10,15,20-tetraaryl-TBP's (Ar4TBP's) were measured. For comparison, similarly meso-arylsubstituted porphyrins fused with nonaromatic cyclohexeno-rings, i.e. Ar(n)-tetracyclohexenoporphyrins (Ar(n)TCHP's, n = 0, 2, 4), were also synthesized and studied. Structural information was obtained by ab initio (DFT) calculations and X-ray crystallography. It was found that: 1) Free-base Ar4TBP's are strongly distorted out-of-plane (saddled), possess broadened, red-shifted spectra, short excited-state lifetimes and low fluorescence quantum yields (tau(fl) = 2-3 ns, phi(fl) = 0.02-0.03). These features are characteristic of other nonplanar free-base porphyrins, including Ar4TCHP's. 2) Ar2TBP free-bases possess completely planar geometries, although with significant in-plane deformations. These deformations have practically no effect on the singlet excited-state properties of Ar2TBP's as compared to planar meso-unsubstituted TBP's. Both types of porphyrins retain strong fluorescence (tau(fl) = 10-12 ns, phi(fl) = 0.3-0.4), and their radiative rate constants (k(r)) are 3-4 times higher than those of planar H2TCHP's. 3) Nonplanar deformations dramatically enhance nonradiative decay of triplet states of regular Pd porphyrins. For example, planar PdTCHP phosphoresces with high quantum yield (phi(phos) = 0.45, tau(phos) = 1118 micros), while saddled PdPh4TCHP is practically nonemissive. In contrast, both ruffled and saddled PdAr(n)TBP's retain strong phosphorescence at ambient temperatures (PdPh2TBP: tau(phos) = 496 micros, phi(phos) = 0.15; PdPh4TBP: tau(phos) = 258 micros, phi(phos) = 0.08). It appears that pi-extension is capable of counterbalancing deleterious effects of nonplanar deformations on triplet emissivity of Pd porphyrins.

The Janus-faced chromophore: a donor-acceptor dyad with dual performance in photon up-conversion.

An electron donor-acceptor dyad based on BODIPY (acceptor) and anthracene (donor) plays either the role of sensitizer or emitter in triplet-triplet annihilation photon up-conversion (TTA-UC). This Janus-like behavior was achieved via altering the relative ordering of charge-transfer and local excited state energies in the dyad through the polarity of TTA-UC media.

Interplay between singlet and triplet excited states in a conformationally locked donor-acceptor dyad.

The synthesis and photophysical characterization of a palladium(II) porphyrin - anthracene dyad bridged via short and conformationally rigid bicyclo[2.2.2]octadiene spacer were achieved. A spectroscopic investigation of the prepared molecule in solution has been undertaken to study electronic energy transfer in excited singlet and triplet states between the anthracene and porphyrin units. By using steady-state and time-resolved photoluminescence spectroscopy it was shown that excitation of the singlet excited state of the anthracene leads to energy transfer to the lower-lying singlet state of porphyrin. Alternatively, excitation of the porphyrin followed by intersystem crossing to the triplet state leads to very fast energy transfer to the triplet state of anthracene. The rate of this energy transfer has been determined by transient absorption spectroscopy. Comparative studies of the dynamics of triplet excited states of the dyad and reference palladium octaethylporphyrin (PdOEP) have been performed.